The Food and Drug Administration gave financial conflict-of-interest waivers to six physicians who will sit on the advisory panel that meets Thursday and Friday to evaluate the safety of drug-eluting stents made by Johnson & Johnson and Boston Scientific. Recent studies have shown that drug-eluting stents, which have been inserted in 4 million Americans with heart disease over the past three years, increase the risk of heart attacks compared to bare-metal stents, which are one-third the cost.

Five of the waivers went to physicians with direct ties to stent manufacturers or makers of drugs used in stents. They included: Richard Page of the University of Washington, who has unrelated consulting agreements with a manufacturer of a drug-eluting stent; George Vetrovec of Virginia Commonwealth University, who has a consulting deal with a manufacturer of drug-eluting stents; Clyde Yancy of the University of Texas Southwestern Medical Center, who has a consulting agreement with a company that makes a drug being tested for use with drug-eluting stents; and Judah Weinberger of Columbia University, who owns stock in companies that manufacture drug-eluting stents. The company names were blacked out in the publicly-released waivers. The FDA also gave JoAnn Lindenfeld of the University of Colorado Health Sciences Center a waiver because she is "recognized as an expert noninvasive cardiologist and heart failure expert and has traditionally served as a useful and thoughtful counterweight to the interventional cardiology perspective." Her waived financial ties included consulting arrangements with an unnamed stent manufacturer and a firm with a competing technology. Earlier this year, she refused to explain to a New York Times reporter her earlier criticism of a cardiovascular device, which had been carried on the specialist-oriented Heartwire. The other financial tie the FDA chose to overlook was Duke University researcher Robert A. Harrington’s consulting arrangements with several drug manufacturers with a stake in continued use of drug-eluting stents. "His views on stent thrombosis and possible mitigation of this devastating complication will be extremely valuable," the FDA waiver said. Earlier this year, Harrington participated in an American College of Cardiology online continuing medical education program that suggested clopidogrel (Sanofi-Aventis' best-selling blood thinner drug Plavix) plus aspirin was better than aspirin alone for preventing blood clots in patients with clogged heart arteries. He disclosed that he or his institution received research grants from 11 firms, including Sanofi-Aventis. A recent New England Journal of Medicine review of the stent issue pointed out that "many physicians now recommend extended or lifetime prescriptions of aspirin and clopidogrel for patients receiving drug-eluting stents."

Science revealed last week that another possible fraudulent paper - this time by a University of Missouri scientist - had slipped through its peer review process, even as an outside panel was suggesting that the magazine establish new procedures to ferret out scientific misconduct. The report, which was commissioned by Science after it learned it had published two fraudulent papers by South Korean stem cell scientist Hwang Woo-Suk, recommended that the magazine develop a "risk assessment" process for identifying high-profile papers in need of extra review. It also called for requiring co-authors to detail their contributions to the work. The recommendation came in response to claims by University of Pittsburgh professor Gerald Schatten, who was lead author on the Hwang paper, that he actually did no work on the study. Science editor-in-chief Donald Kennedy said the journal is developing the criteria outlined in the report.

Missing from the report, however, was a call for deeper scrutiny of conflicts of interest, despite the fact neither Hwang nor Schatten revealed that they held patents in the stem cell technologies discussed in their paper. Kennedy also failed to address the two scientists' fraudulent conflict-of-interest disclosure. Meanwhile, last week's issue of Science reported on the ongoing investigation into a University of Missouri-Columbia paper by animal science professor R. Michael Roberts, which was published in Science earlier this year. His paper, which claims mammalian embryo cell differentiation occurs earlier than previously thought, which could have significant implications for animal cloning, may have used manipulated photos, a tactic also employed by Hwang. Science warned that the results should not be trusted, but has not yet retracted the study. Roberts holds two active patents for technologies developed through his research and has received funding from six biotechnology companies. It is unclear whether these activities are related to the Science report, which did not disclose any of Roberts' financial ties

Did a Study of Glaxo's New Herpes Drug Mistreat Pregnant Women?

A study that appeared in the July issue of Obstetrics & Gynecology showed that pregnant women with recurrent genital herpes who use GlaxoSmithKline's new anti-herpes drug valacyclovir (Valtrex) during the last weeks of pregnancy undergo fewer cesarean deliveries to avoid mother-child transmission. But in the latest issue of the journal, two OB/GYNs and Public Citizen accuse the study's authors of ignoring the patient protection rules in the Declaration of Helsinki by not offering the 168 women in the placebo arm of the trial a drug that was already known to be effective for the condition, the off-patent drug acyclovir. Valacyclovir, which is still on patent, turns into acyclovir once it is in the body. "We are at a loss as to why researchers would place their patients at higher risk," wrote Aaron B. Caughey of the University of California at San Francisco, Adam C. Urato of the University of South Florida, and Peter Lurie of Public Citizen.

Guidelines published by the American College of Obstetrics and Gynecology in 1999 called for using acyclovir. The authors of the recent study wrote a review in 2003 calling for using acyclovir. Recruitment of patients took place between 1998 and 2004. But in their response, the original study's authors, who included Glaxo speakers bureau member George D. Wendel of the University of Texas Southwestern Medical Center, backtracked on that earlier paper. Guidelines from the Centers for Disease Control and the American Academy of Pediatrics do not specifically recommend using acyclovir, they responded. Moreover, the latest study, "Valacyclovir Prophylaxis to Prevent Recurrent Herpes at Delivery," was really designed to test the drug's impact on the baby, which could only be done in a placebo-controlled trial. "The consideration of fetal risks and benefits . . . was a fundamental issue for us as we designed and conducted this trial," they wrote.

Blackwell Publishing, which publishes over 800 academic journals, last week announced new guidelines on publication ethics, including strict conflict-of-interest disclosure rules. Drawn largely from guidelines issued by the International Committee of Medical Journal Editors, the suggested policies also cover hot button issues like data transparency and registering clinical trials. While the guidelines are not mandatory (Blackwell specializes in handling journals for professional and academic societies), the company plans to launch a major campaign to convince editors and societies to adopt the policies. The Center for Science in the Public Interest offered comments on an early version of the guidelines.

The conflict of interest disclosure section recommends that author statements include all financial interests that occurred in the past three years that are relevant to the study, "but relevant conflicts of interest that are older should not be neglected." The rules should cover any type of article, including research, reviews, letters and commentaries. In confirmed cases of author misconduct, such as failure to disclose relevant conflicts of interest, journals "may consider imposing sanctions on the authors at fault for a period of time . . . (including) refusal to accept future submissions from the individual, unit or institution responsible for the misconduct, for a stated period." The guidelines also addressed supplements, suggesting journals disclose conflicts of interest for all authors and editors, as well as the "description of the processes used to select, review and edit the content, especially the differences in this process, if there are any, from the journal's normal content selection and peer-review processes."

Pfizer, Scripps Research Institute in Sweetheart IP Deal

Pfizer Inc., the world's largest drug company, last week donated $100 million over five years to the Scripps Research Institute in exchange for first rights to nearly half the intellectual property generated by the grants. The deal replaces a similar 10-year partnership with Novartis that expires at the end of December, according to the San Diego Union-Tribune. The non-profit Scripps, which is based in La Jolla, generates 75 percent of its $350 million budget from the National Institutes of Health. Two years ago it received over $500 million in tax subsidies to expand its operations into Florida. Congress investigated Scripps' earlier deal with Novartis (it was then known as Sandoz) because it steered research priorities and excluded small firms from competing for patent licenses. While Pfizer still gets preferential IP treatment, this latest five-year deal does not allow the company to designate specific research projects. NIH will also get to approve the final contract, a Scripps spokesman told the paper.

Urologists Turn to Profitable Therapy for Prostate Cancer

A radiation therapy for prostate cancer that is more than twenty times as profitable as traditional treatments is growing in popularity, even though there is little consensus about its scientific benefits, the New York Times reported last week. The financial incentives are raising concerns that urologists may be more likely to recommend the treatment, known as intensity modulated radiation therapy (IMRT), over other proven approaches, including forgoing treatment. Urologists using IMRT can receive reimbursements of more than $47,000 from insurance companies and Medicare, compared to $2,000 or less for surgery or other radiation treatments. In a marketing pitch to doctors, Texas-based Urorad Healthcare, which sells IMRT technology and services, touts the economic advantages of the treatment as one of its major selling points. "Join the Urorad team and let us show your group how Urorad clients double their practice's revenue," the company says on its Web site.

The Sun Fails to Disclose Doctor's Funding from Vaccine Industry

In a story on the seasonal flu epidemic, The Baltimore Sun failed to disclose the numerous financial ties to the vaccine industry of a doctor they quoted. In the story, James Cherry, physician and professor at the University of California, Los Angeles, refuted claims that a lack of vitamin D, provided in large part by sunlight, could account for the spike in influenza during dark winter months. The Sun failed to mention that since 1981, Cherry has made approximately $50,000 per year testifying for diphtheria, tetanus, pertussis (DPT) vaccine manufacturers, at a rate of $200 per hour, for 90 different cases. He has also received almost $550,000 in research funding from Lederle Laboratories, maker of a DTP vaccine, and his department has received $654,418 from the same company for vaccine research. In addition, Cherry sits on advisory boards for the American Academy of Pediatrics and the Centers for Disease Control. In 1991, the National Vaccine Information Center, a non-profit educational organization, asked Cherry and a colleague to resign, citing their conflicts of interest for receiving more than $800,000 in expert witness fees, consulting fees, and research grants from DTP vaccine manufacturers.

Dems Express 'Serious Concerns' About EPA Library Closures

Four incoming House committee chairmen last week called on the Environmental Protection Agency to immediately stop efforts to close agency libraries pending a congressional investigation. In a Nov. 30 letter to EPA Administrator Stephen Johnson, Democrats who will chair the Science, Energy and Commerce, Government Reform, and Transportation committees warned that the agency's actions threaten to dismantle "what is likely one of our country's most comprehensive and accessible collections of environmental materials." The letter comes on the heels of an attempt by Senate Democrats to get the Appropriations Committee to restore funding for EPA's library collections, citing concerns from agency staff that the closures may hamper responses to emergencies and undercut its rulemaking abilities.

Odds and Ends

Los Angeles-based Environment California released a report last week that found perchlorate producers funded more than half of all scientific studies on the health effects of perchlorate exposure as part of a campaign to downplay concerns about rocket fuel pollution . . . The presidents of five unions representing more than 10,000 EPA scientists petitioned Congress to address global warming and called for an end to censorship of agency scientists . . . Today's Washington Post article on endocrine disruptors quoted Texas A &M professor Stephen H. Safe's doubts about the threats posed by industrial chemicals without noting that the American Chemistry Council is a major funder of his research.

The Integrity in Science Database of Scientists and Organizations WIth Ties to Industry can be found at: www.integrityinscience.org.
Please circulate. To subscribe to Integrity in Science Watch or to send tips for inclusion in the Database, please send an email to science@cspinet.org.
If you do not wish to receive these emails, please hit reply and put "unsubscribe" in the subject line. If you receive duplicate emails from Integrity Watch, please hit reply and type "duplicate" in the subject line.